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Dulaglutide Effect on Proteins Associated With CKD Progression.
Brandon E McFarlin1, Sok Cin Tye2,3, Eiichiro Satake2,3
1Diabetes, Obesity, and Complications Research Division, Eli Lilly and Company, Indianapolis, Indiana, USA.
Kidney International Reports
|February 24, 2026
Summary
Dulaglutide treatment in type 2 diabetes patients with chronic kidney disease significantly reduced 14 kidney injury proteins, particularly those linked to inflammation. These findings suggest dulaglutide
Area of Science:
- Nephrology and Endocrinology
- Molecular Biology and Proteomics
Background:
- Type 2 diabetes mellitus (T2D) and chronic kidney disease (CKD) are significant health concerns.
- The AWARD-7 trial demonstrated dulaglutide's renoprotective effects in T2D patients with moderate-to-severe CKD.
- Understanding the molecular mechanisms behind dulaglutide's efficacy is crucial for managing kidney disease progression.
Purpose of the Study:
- To investigate the impact of once-weekly dulaglutide versus insulin glargine on plasma concentrations of 21 key proteins associated with end-stage kidney disease (ESKD) risk.
- To explore potential biological pathways mediating the renoprotective effects of dulaglutide in T2D patients with CKD.
Main Methods:
- A post hoc analysis of the AWARD-7 clinical trial data was performed.
- Plasma samples from participants treated with dulaglutide (n=124) or insulin glargine (n=125) were analyzed using a customized Joslin OLINK proteomic platform.
- Changes in 21 Joslin Kidney Panel (JKP) protein concentrations from baseline to 6 months were measured and compared between treatment groups.
Main Results:
- After 6 months, 14 JKP proteins showed significant differences between dulaglutide and insulin glargine groups.
- Dulaglutide treatment led to a decrease in these 14 JKP proteins, while insulin glargine treatment led to an increase.
- Notably, 8 tumor necrosis factor (TNF)-receptors and other proteins involved in inflammatory and fibrotic pathways were significantly affected by dulaglutide.
Conclusions:
- Six months of dulaglutide treatment significantly reduced plasma concentrations of 14 JKP proteins, particularly those in inflammatory and fibrotic pathways.
- These proteomic changes provide novel insights into the biological mechanisms underlying dulaglutide's renoprotective effects in T2D patients with CKD.
- The findings support dulaglutide as a therapeutic option for slowing kidney function decline in this patient population.
Keywords:
biomarkerschronic kidney diseasediabetesdulaglutideglucagon-like peptide-1 (GLP-1) receptor agonistsMore Related Videos
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